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Publication
Circadian control of bile acid synthesis by a KLF15-Fgf15 axis.
Authors Han S, Han SS, Zhang R, Jain R, Shi H, Zhang L, Zhou G, Sangwung P, Tugal D,
Atkins GB, Prosdocimo DA, Lu Y, Han X, Tso P, Liao X, Epstein JA, Jain MK
Submitted By Mukesh Jain on 2/19/2016
Status Published
Journal Nature communications
Year 2015
Date Published
Volume : Pages 6 : 7231 - 7
PubMed Reference 26040986
Abstract Circadian control of nutrient availability is critical to efficiently meet the
energetic demands of an organism. Production of bile acids (BAs), which
facilitate digestion and absorption of nutrients, is a major regulator of this
process. Here we identify a KLF15-Fgf15 signalling axis that regulates circadian
BA production. Systemic Klf15 deficiency disrupted circadian expression of key
BA synthetic enzymes, tissue BA levels and triglyceride/cholesterol absorption.
Studies in liver-specific Klf15-knockout mice suggested a non-hepatic basis for
regulation of BA production. Ileal Fgf15 is a potent inhibitor of BA synthesis.
Using a combination of biochemical, molecular and functional assays (including
ileectomy and bile duct catheterization), we identify KLF15 as the first
endogenous negative regulator of circadian Fgf15 expression. Elucidation of this
novel pathway controlling circadian BA production has important implications for
physiologic control of nutrient availability and metabolic homeostasis.




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